Botanical Breakthroughs in Depression: Insights from the Cums Animal Model

Depression is a debilitating mental health condition with significant global prevalence and a profound impact on quality of life. Conventional antidepressant therapies, though effective in many cases, are often limited by delayed onset of action, side effects, and treatment resistance. Consequently, the exploration of alternative and complementary approaches, particularly those involving medicinal plants, has gained momentum in recent years. The Chronic Unpredictable Mild Stress (CUMS) model, widely used to simulate human depression in animal studies. Numerous medicinal plants have demonstrated promising antidepressant-like effects in this model, often by modulating key neurobiological pathways, such as monoaminergic transmission, hypothalamic-pituitary- adrenal (HPA) axis activity, oxidative stress, neuroinflammation, and neurotrophic factor expression (notably Brain-Derived Neurotrophic Factor, BDNF). These botanicals often exhibit multi-targeted effects, making them attractive candidates for integrative therapeutic approaches. This review highlights the evaluation of antidepressant activity of various medicinal plants extracts by specifically applying chronic unpredictable mild stress (CUMS) for particular period of time including mechanisms of action, behavioral models used (e.g., FST, TST, SPT), and comparative efficacy of various plant extracts in the CUMS model, underlining the potential of phytomedicines as viable alternatives or adjuncts in depression management.